In recent years, there has been increasing interest in nanotechnology, and novel functional materials utilizing properties unique to nanosized substances have been developed. Such novel functional materials can be applied to a wide variety of fields such as energy, electronics, and medical and pharmaceutical fields. Among them, nanotechnology has received attention for the detection of substances in biological samples and in vivo imaging.
In medical and pharmaceutical fields, attention has been given to a near-infrared fluorescence photography method for imaging a tumor site by accumulation of a near-infrared fluorescent dye in the tumor site. In this method, a compound having the property of emitting fluorescence in the near-infrared region by irradiation with excitation light is administered as an imaging agent to a living body. Then, the living body is externally irradiated with excitation light having a near-infrared wavelength, and fluorescence emitted from the fluorescent imaging agent accumulated in a tumor site is detected to determine a lesion site.
A substance used as an imaging probe is mainly composed of a carrier agent and a fluorescent dye, and various carrier agents and fluorescent dyes have been reported.
Examples of the carrier agent include a liposome nanoparticle (JP-A-2005-220045 (Patent Document 1)), a peptidic nanoparticle (Journal of Controlled Release 51 (1998) 241-248 (Non-Patent Document 1)), a nanoparticle using an amphiphilic block polymer having, as a hydrophobic block, poly glutamic acid methyl ester (JP-A-2008-024816 (Patent Document 2)), a nanoparticle using an amphiphilic block polymer composed of a polysarcosine chain and a polylactic acid chain (Chemistry Letters, vol. 36, no. 10, 2007, p. 1220-1221 (Non-Patent Document 2)), and a nanoparticle using an amphiphilic block polymer composed of a polysarcosine chain and a polylactic acid chain, and a polylactic acid (WO 2009/148121 (Patent Document 3)).
The fluorescent dye is covalently bound to or non-covalently encapsulated in the carrier agent, and a fluorescein-based dye, a cyanine-based dye, a rhodamine-based dye, or the like is used. As the cyanine-based dye, indocyanine green (ICG) is often used, but various indocyanine derivatives have been developed (Bioconjugate Chem. 1996, 7, 356-362 (Non-Patent Document 3), The 131st Annual Meeting of The Pharmaceutical Society of Japan, 29p-am395Q poster, Mar. 29, 2010 (Non-Patent Document 4)). Further, methods have been reported which allow nanoparticles quenched by encapsulation of both an indocyanine derivative and a quencher to acquire fluorescence when the nanoparticles reach a tumor tissue (Cancer Research, 60, 4953-4958, Sep. 1, 2000 (Non-Patent Document 5), Bioconjugate Chem. 2002, 13, 605-610 (Non-Patent Document 6), Cancer Research, 2009; 69: (4). Feb. 15, 2009 (Non-Patent Document 7)).
More specifically, Non-Patent Document 4 described above discloses the preparation of nanoparticles IC7-1 lactosome from 500 μL of a 6 mg/mL solution of an amphiphilic polymer composed of a polysarcosine chain and a polylactic acid chain (PSar70-PLLA30), and 3.16 μL of a 1 mg/mL solution of an indocyanine derivative IC7-1. That is, it has been disclosed that the amount of the indocyanine derivative IC7-1 encapsulated in the nanoparticle IC7-1 lactosome is 0.48 mol %. This amount of the encapsulated indocyanine derivative IC7-1 corresponds to 1 molecule per single nanoparticle IC7-1 lactosome.